Progress in Whole Genome Sequencing (WGS) has had a dramatic impact on bacterial epidemiology. It has become possible to reconstruct outbreaks and epidemics in unprecedented detail. WGS also allows linking genotypes to phenotypes and has been surprisingly effective in the context of diagnosing Anti-Microbial Resistance (AMR), with AMR profiles inferred from sequence data being increasingly more accurate and cost-effective than those obtained through classical microbiology. In the first part of the talk, I will illustrate the progress in the field with some recent examples on MRSAs and Mycobacterium tuberculosis. What is less widely acknowledged is that such successes are largely limited to “clonal” organisms such as MRSA and Mycobacteria. In the second part of the talk I will discuss some of the conceptual and computational challenges that lie ahead before we can hope to replicate the successes in the genetic epidemiology of “clonal” bacteria to microbes with extensive recombination, large accessory genomes and resistance determinants situated on plasmids.